Folding helical proteins in explicit solvent using dihedral-biased tempering.

Using a single-trajectory-based tempering method with a high-temperature dihedral bias, we repeatedly folded four helical proteins [α(3)D (PDB ID: 2A3D, 73 residues), α(3)W (1LQ7, 67 residues), Fap1-NR(α) (2KUB, 81 residues) and S-836 (2JUA, 102 residues)] and some of the mutants in explicit solvent within several microseconds. The lowest root-mean-square deviations of backbone atoms from the experimentally determined structures were 1.9, 1.4, 1.0, and 2.1 Å, respectively. Cluster analyses of folding trajectories showed the native conformation usually occupied the most populated cluster. The simulation protocol can be applied to large-scale simulations of other helical proteins on commonly accessible computing platforms.